12-20813614-C-T

Position:

• chr12-20813614-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019844.4(SLCO1B3):​c.-90C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,032 control chromosomes in the GnomAD database, including 33,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33518 hom., cov: 33)
  • Exomes 𝑓: 0.60 (2 hom.)
• Consequence: SLCO1B3 NM_019844.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.937

Genes affected

SLCO1B3 (HGNC:10961): (solute carrier organic anion transporter family member 1B3) This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia. Alternative splicing of this gene and the use of alternative promoters results in transcript variants encoding different isoforms that differ in their tissue specificity. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-20813614-C-T is Benign according to our data. Variant chr12-20813614-C-T is described in ClinVar as [Benign]. Clinvar id is 307884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B3	NM_019844.4	c.-90C>T		5_prime_UTR_variant	2/16	ENST00000381545.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.-90C>T		5_prime_UTR_variant	2/16	2	NM_019844.4	P1
SLCO1B3	ENST00000540853.5	c.-65-2060C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100365 AN: 151904 Hom.: 33496 Cov.: 33

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.652

GnomAD4 exome AF: 0.600 AC: 6 AN: 10 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.625

GnomAD4 genome AF: 0.661 AC: 100430 AN: 152022 Hom.: 33518 Cov.: 33 AF XY: 0.666 AC XY: 49518 AN XY: 74320

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.652

Alfa AF: 0.663 Hom.: 4211

Bravo AF: 0.658

Asia WGS AF: 0.781 AC: 2716 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rotor syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7305323; hg19: chr12-20966548;